Stress-related Signaling Research Articles

Bacopa monnieri Extract Diminish Hypoxia-Induced Anxiety by Regulating HIF-1α Signaling and Enhancing the Antioxidant Defense System in Hippocampus.

Hypoxia is a significant stressor, and stabilized hypoxia-inducible factor-1α (HIF-1α) regulates the expression of numerous genes, leading to various biochemical, molecular, physiological and genomic changes. The body's oxygen-sensing system activates gene expression to protect brain tissues from hypoxia. Gamma-aminobutyric acid, an inhibitory neurotransmitter, regulates brain excitability during hypoxia through the activation of HIF-1 α. Herbal medicines have been widely used for managing various toxicological effects and disorders including hypoxia; however, the data on safety, efficacy and the molecular mechanisms that increase vulnerability or lethality against hypoxia are still lacking and urgently need to be investigated. The Current study aims to investigate how Bacopa monnieri extract (BME), specially CDRI-08 affects the hippocampus of mice subjected to conditions that simulate hypoxia. The pre and co-treatment of mice involved administrating BME (200mg/kg BW) for 14days, followed by exposure to CoCl2 (40mg/kg BW). BME decreased the levels of reactive oxygen species (ROS) and lipid peroxidation, while it increased the Gamma-aminobutyric acid receptor subunit-ɑ1 (GABAAR-ɑ1) level as well as the activity of antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx). Furthermore BME reduced the levels of HIF-1α and its downstream targets glucose transporter-1 (GLUT-1) and erythropoietin (EPO) in the DG, CA1, and CA3 regions of hippocampus. Additionally, results obtained from the open field, elevated zero maze and plus maze tests indicate that BME restores anxiety caused by hypoxia. Together, these findings suggested that BME mitigates the harmful effects of oxidative stress and altered hypoxia related signaling in hippocampus; and may provide a basis for its therapeutic use in the recovery from hypoxia-led anxiety.

The ASPARAGINE-RICH PROTEIN-LYST-INTERACTING PROTEIN5 complex regulates non-canonical AUTOPHAGY8 degradation in Arabidopsis.

The endocytic and autophagic pathways play important roles in abiotic stress responses and maintaining cellular homeostasis in plants. Asparagine Rich Proteins (NRPs) are plant-specific stress-responsive proteins that are involved in many abiotic stress-related signaling pathways. We previously demonstrated that NRP promotes PIN FORMED 2 (PIN2) vacuolar degradation to maintain PIN2 homeostasis under abscisic acid (ABA) treatment in Arabidopsis (Arabidopsis thaliana). However, the molecular function and mechanism of NRP in cellular vesicle trafficking remain unknown. In this study, we report that NRP directly interacts with LIP5 and ATG8, critical components of the endocytic and autophagic pathways, respectively. Genetic analyses show that NRP overexpression rescues canonical autophagy defects in a LIP5-dependent manner. Cellular and biochemical evidence indicates that NRP-LIP5 recruits ATG8 to multivesicular bodies for further vacuolar degradation, implying that a novel NRP-mediated endocytic pathway is utilized to compensate for the canonical autophagy defects that occur during plant stress responses. These findings provide insights into the crosstalk between the endocytic and autophagic pathways and uncover a function of ATG8 distinct from its canonical role in autophagy. The mechanism revealed here confers an evolutionary advantage to plants and provides a molecular basis for breeding crops with greater stress tolerance.

Identification and functional analyses of drought stress resistance genes by transcriptomics of the Mongolian grassland plant Chloris virgata

BackgroundMongolian grasslands, including the Gobi Desert, have been exposed to drought conditions with few rains. In such harsh environments, plants with highly resistant abilities against drought stress survive over long periods. We hypothesized that these plants could harbor novel and valuable genes for enhancing drought stress resistance.ResultsIn this study, we identified Chloris virgata, a Mongolian grassland plant with strong drought resistance. RNA-seq-based transcriptome analysis was performed to uncover genes associated with drought stress resistance in C. virgata. De novo transcriptome assembly revealed 25,469 protein-coding transcripts and 1,219 upregulated genes after 3- and 6-hr drought stress treatments. Analysis by homology search and Gene Ontology (GO) enrichment indicated that abscisic acid (ABA)- and drought stress-related GO terms were enriched. Among the highly induced genes, ten candidate cDNAs were selected and overexpressed in Arabidopsis. When subjected to drought stress, three of these genes conferred strong drought resistance in the transgenic plants. We named these genes Mongolian Grassland plant Drought-stress resistance genes 1, 2, and 3 (MGD1, MGD2, and MGD3). Gene expression analyses in the transformants suggested that MGD1, MGD2, and MGD3 may activate drought stress-related signalling pathways.ConclusionThis study highlighted the drought resistance of C. virgata and identified three novel genes that enhance drought stress resistance.

Chemoresistance in Pancreatic Cancer: The Role of Adipose-Derived Mesenchymal Stem Cells and Key Resistance Genes.

Drug resistance is a significant challenge in pancreatic ductal adenocarcinoma (PDAC), where stromal elements such as adipose-derived mesenchymal stem cells (ASCs) contribute to a chemoresistant tumor microenvironment (TME). This study explored the effects of oxaliplatin (OXP) and 5-fluorouracil (5-FU) on PDAC cells (Capan-1) and ASCs to investigate the mechanisms of chemoresistance. While OXP and 5-FU reduced Capan-1 viability in a dose- and time-dependent manner, ASCs demonstrated high resistance, maintaining > 90% viability even at cytotoxic doses. Transcriptomic analyses revealed OXP-induced transcriptional reprogramming in ASCs, with over 7000 differentially expressed genes, highlighting the pathways related to DNA damage response, cell cycle regulation, and stress-related signaling. In contrast, 5-FU elicited limited transcriptional changes, affecting only 192 genes. Cytokine proteome profiling revealed that OXP-treated ASCs significantly influenced the tumor microenvironment by promoting immune evasion (via IL-4, GM-CSF, IP-10, and GROα) and driving extracellular matrix remodeling (through EMMPRIN and DPPIV). In contrast, 5-FU induced comparatively weaker effects, primarily limited to hypoxia-related pathways. Although OXP reduced angiogenic factors, it paradoxically activated pro-survival pathways, thereby enhancing ASC-mediated tumor support. These findings underscore ASCs as modulators of chemoresistance via secretome alterations and stress adaptation. Therefore, future strategies should prioritize the precise targeting of tumor cells while also focusing on the development of personalized treatments to achieve durable therapeutic responses in PDAC.

SKA2 enhances stress-related glucocorticoid receptor signaling through FKBP4–FKBP5 interactions in neurons

Genes involved in regulating the hypothalamic-pituitary-adrenal (HPA) axis, including the glucocorticoid receptor (GR), are linked to various stress-related psychopathologies including bipolar disorder as well as other mood and trauma-related disorders. The protein product of the cell cycle gene, SKA2, is a GR interaction partner in peripheral cells. However, the precise roles of SKA2 in stress and GR signaling in the brain, specifically in nonreplicating postmitotic neurons, and its involvement in HPA axis regulation remain unclear. Here, we demonstrate, using diverse in vitro cell assays, a mechanism by which SKA2 promotes GR signaling through enhancing GR-FKBP4 interaction leading to dissociation of FK506-bindingprotein 51 (FKBP5) from the complex. FKBP4 and FKBP5 are cochaperones known to regulate GR function in opposite directions. Notably in mice, SKA2 in Crh+ neurons of the paraventricular nucleus of the hypothalamus is crucial for HPA axis responsiveness and for maintaining the negative feedback loop underlying allostasis. Moreover, we show that SKA2 expression is increased in postmortem human hippocampus and amygdala from individuals with BD. Our study highlights a critical role of SKA2 in HPA axis function, adds to the understanding of the molecular basis of stress-related psychiatric disorders, and points to potential targets for intervention.

Quercetin Alleviates All-Trans-Retinal-Induced Photoreceptor Apoptosis and Retinal Degeneration by Inhibiting the ER Stress-Related PERK Signaling.

All-trans-retinal (atRAL)-induced photoreceptor atrophy and retinal degeneration are hallmark features of dry age-related macular degeneration (AMD) and Stargardt disease type 1 (STGD1). The toxicity of atRAL is closely related to the generation of reactive oxygen species (ROS). Quercetin, a natural product, is known for its potent antioxidant properties; however, its effects in mitigating atRAL-mediated retinal damage remains unclear. This study investigated the protective effects of quercetin against atRAL-induced photoreceptor damage. Using atRAL-loaded 661W photoreceptor cells, we evaluated cell viability, ROS generation, and endoplasmic reticulum (ER) stress under quercetin treatment. Quercetin significantly restored the cell viability (to 70%) and reduced ROS generation in atRAL-treated 661W cells. Additionally, Western blot analysis demonstrated that quercetin mitigated protein kinase RNA-like ER kinase (PERK) signaling, preventing ER stress-induced apoptosis. Importantly, in Abca4-/-Rdh8-/- mice, an animal model of light-induced atRAL accumulation in the retina, quercetin treatment effectively alleviated light-exposed photoreceptor atrophy and retinal degeneration by attenuating PERK signaling. Thus, quercetin protected photoreceptor cells from atRAL-induced damage by inhibiting ROS generation and PERK signaling, which suggests its potential as a therapeutic agent for atRAL-related retinal degeneration.

Senescence and Stress Signaling Pathways in Corneal Cells After Nitrogen Mustard Injury.

Mustard gas keratopathy (MGK), a complication of exposure to sulfur mustard, is a blinding ocular surface disease involving key cellular pathways, including apoptosis, oxidative stress, and inflammation. Recent studies indicate that cellular senescence contributes to the pathophysiology of mustard gas toxicity. This study aimed to assess senescence and stress-related pathways-particularly mitogen-activated protein kinase (MAPK) signaling-in nitrogen mustard (NM)-induced corneal injury. In vitro, primary human corneal epithelial (P-HCECs), primary human corneal mesenchymal stromal cells (hcMSCs), and human corneal-limbal epithelial cell (HCLE) lines were exposed to varying concentrations of NM. The results demonstrated a dose-dependent increase in cellular senescence, characterized by reduced Ki67 expression, elevated p16, and p21 mRNA levels, as well as activation of the MAPK pathway activation. Treatment with a selective p38-MAPK inhibitor significantly reduced senescence markers and improved cell proliferation following exposure to NM. Overall, these studies indicate that NM exposure triggers cellular senescence and stress-related MAPK signaling, while p38-MAPK inhibition mitigates these effects, suggesting a potential therapeutic strategy.

Genome-wide analysis and expression profiling of the polyamine oxidase gene family in Solanum tuberosum L.

BackgroundPolyamine oxidase (PAO) is a crucial enzyme involved in the breakdown of polyamines (PAs) in plants. It not only regulates the levels of PAs, but also plays a role in the oxidative decomposition of PAs and the release of stress-related signals, contributing to the plant’s response and resistance to various adversities. While there have been numerous studies on the response of PAO to stress in other crops, there is a lack of research on this topic in potatoes, a major food crop.ResultsIn this study, we aimed to explore the biological function of the StPAO gene in potato growth and development, as well as its expression patterns under stress. Using bioinformatics methods, we identified 14 StPAO genes in the potato genome. Protein sequence comparisons revealed a high similarity between the PAO proteins of potato and Arabidopsis. Chromosomal mapping and gene structure analysis showed that the StPAO genes were not evenly distributed on the chromosome and all contained an amino-oxidase domain. Furthermore, analysis of the promoters of these genes revealed the presence of abiotic and stress-related cis-acting elements, indicating their potential role in responding to different stresses. To investigate the expression patterns of these genes under stress, we used qRT-PCR to study their response to high temperature, drought, and ABA stress. Our results showed that StPAO6 and StPAO10 were significantly up-regulated under high temperature stress, indicating that they were involved in the process of potato resistance to high temperatures. Similarly, StPAO1, StPAO3, and StPAO4 were significantly up-regulated under drought stress, indicating their potential role in potatoes’ responses to drought. After ABA treatment, the expression levels of StPAO4, StPAO5, StPAO7, and StPAO14 were significantly up-regulated, suggesting their involvement in chemical defense mechanisms. Interestingly, the expression of StPAO11–13 was inhibited by all three stresses.ConclusionsIn conclusion, our study highlights the multifunctional nature of the StPAO gene family in potatoes, which plays a crucial role in coping with various stresses. This research deepens our understanding of the potato StPAO gene family and provides a reference for future studies on its function. It also serves as a theoretical basis for breeding stress-resistant potato varieties in the future.

Research progress on metal pollutants inducing neurotoxicity through ferroptosis

It has been confirmed that exposure to various metal pollutants can induce neurotoxicity, which is closely associated with the occurrence and development of neurological disorders. Ferroptosis is a form of cell death in response to metal pollutant exposure and it is closely related to oxidative stress, iron metabolism and lipid peroxidation. Recent studies have revealed that ferroptosis plays a significant role in the neurotoxicity induced by metals such as lead, cadmium, manganese, nickel, and antimony. Lead exposure triggers ferroptosis through oxidative stress, iron metabolism disorder and inflammation. Cadmium can induce ferroptosis through iron metabolism, oxidative stress and ferroptosis related signaling pathways. Manganese can promote ferroptosis through mitochondrial dysfunction, iron metabolism disorder and oxidative stress. Nickel can promote ferroptosis by influencing mitochondrial function, disrupting iron homeostasis and facilitating lipid peroxidation in the central nervous system. Antimony exposure can induce glutathione depletion by activating iron autophagy, resulting in excessive intracellular iron deposition and ultimately causing ferroptosis. This article reviews the effects of metal pollutants on ferroptosis-related indicators and discusses the specific mechanisms by which each metal triggers ferroptosis. It provides a reference for identifying targets for preventing neurotoxicity and for developing treatment strategies for neurological disorders.

Metabolic pathways, genomic alterations, and post-translational modifications in pulmonary hypertension and cancer as therapeutic targets and biomarkers.

Pulmonary hypertension (PH) can lead to right ventricular hypertrophy, significantly increasing mortality rates. This study aims to clarify PH-specific metabolites and their impact on genomic and post-translational modifications (PTMs) in cancer, evaluating DHA and EPA's therapeutic potential to mitigate oxidative stress and inflammation. Data from 289,365 individuals were analyzed using Mendelian randomization to examine 1,400 metabolites' causal roles in PH. Anti-inflammatory and antioxidative effects of DHA and EPA were tested in RAW 264.7 macrophages and cancer cell lines (A549, HCT116, HepG2, LNCaP). Genomic features like CNVs, DNA methylation, tumor mutation burden (TMB), and PTMs were analyzed. DHA and EPA's effects on ROS production and cancer cell proliferation were assessed. We identified 57 metabolites associated with PH risk and examined key tumor-related pathways through promoter methylation analysis. DHA and EPA significantly reduced ROS levels and inflammatory markers in macrophages, inhibited the proliferation of various cancer cell lines, and decreased nuclear translocation of SUMOylated proteins during oxidative stress and inflammatory responses. These findings suggest a potential anticancer role through the modulation of stress-related nuclear signaling, as well as a regulatory function on cellular PTMs. This study elucidates metabolic and PTM changes in PH and cancer, indicating DHA and EPA's role in reducing oxidative stress and inflammation. These findings support targeting these pathways for early biomarkers and therapies, potentially improving disease management and patient outcomes.

Molecular Communication of Microbial Plant Biostimulants in the Rhizosphere Under Abiotic Stress Conditions.

Microbial plant biostimulants offer a promising, sustainable solution for enhancing plant growth and resilience, particularly under abiotic stress conditions such as drought, salinity, extreme temperatures, and heavy metal toxicity. These biostimulants, including plant growth-promoting rhizobacteria, mycorrhizal fungi, and nitrogen-fixing bacteria, enhance plant tolerance through mechanisms such as phytohormone production, nutrient solubilization, osmotic adjustment, and antioxidant enzyme activation. Advances in genomics, metagenomics, transcriptomics, and proteomics have significantly expanded our understanding of plant-microbe molecular communication in the rhizosphere, revealing mechanisms underlying these interactions that promote stress resilience. However, challenges such as inconsistent field performance, knowledge gaps in stress-related molecular signaling, and regulatory hurdles continue to limit broader biostimulant adoption. Despite these challenges, microbial biostimulants hold significant potential for advancing agricultural sustainability, particularly amid climate change-induced stresses. Future studies and innovation, including Clustered Regularly Interspaced Short Palindromic Repeats and other molecular editing tools, should optimize biostimulant formulations and their application for diverse agro-ecological systems. This review aims to underscore current advances, challenges, and future directions in the field, advocating for a multidisciplinary approach to fully harness the potential of biostimulants in modern agriculture.

The TSH Receptor Antibody Reactome Contributes to Retro-Orbital Inflammation.

The thyroid eye disease (TED) of Graves disease is associated with high titers of stimulating TSH receptor antibodies, retro-orbital inflammation, fibroblast release of cytokines and chemokines, and adipogenesis, which in turn leads to proptosis, muscle fibrosis, and dysfunction. Part of this scenario is the induction of fibroblast proliferation and autophagy secondary to synergism between the TSH receptor (TSHR) and the insulin-like growth factor-1 receptor (IGF-1R). While TED is well associated with thyroid-stimulating antibodies to the TSHR, which is also well expressed on fibroblasts, in fact the TSHR reactome has a variety of TSHR antibodies with varying biological activity. Therefore, we have now evaluated the possible role of neutral TSHR antibodies (N-TSHR-mAbs), directed at the hinge region of the TSHR, which do not induce cell proliferation but are known to have effects on multiple proteins in thyroid cells including stress-related signaling molecules. We examined the consequences of an N-TSHR-mAb acting on TSHR-expressing fibroblasts and found marked cell stress, which initiated signaling pathways involving inflammasome activation. This response ended in widespread cell death by pyroptosis through activation of caspase 8 and gasdermin D. Hence, not only can stimulating TSHR autoantibodies influence TED inflammation but the N-TSHR antibodies, representing more of the reactome, may also exaggerate the retro-orbital inflammatory response seen in TED.

Sodium butyrate alleviates T-2 toxin-induced liver toxicity and renal toxicity in quails by modulating oxidative stress-related Nrf2 signaling pathway, inflammation, and CYP450 enzyme system.

T-2 toxin is a member of class A aspergilloides toxins, one of the most prevalent mycotoxins that contaminate feed and food. Direct ingestion of animals or feed contaminated by T-2 toxin can cause various animal diseases. Butyrate is an organic fatty acid featuring a four-carbon chain, which is commonly found in the form of sodium butyrate (NaB). NaB has several biological functions and pharmacological effects. However, the role of sodium butyrate in alleviating T-2 toxin-induced hepatorenal toxicity has not been explored. In this study, 240 juvenile quails were evenly assigned into 4 groups. The experimental setup comprised four groups: The control group received a standard diet; the toxin group received a diet containing 0.9mg/kg T-2 toxin; the butyrate group received a diet containing 0.5g/kg NaB; and the T-2 treatment group received a diet containing both 0.9mg/kg T-2 toxin and 0.5g/kg NaB. We evaluated the histopathological changes in the kidney and liver on Days 14 and 28 and explored the molecular mechanisms involving oxidative stress, inflammation, and expression of nuclear xenobiotic receptors (NXRs). Our results showed that T-2 toxin exposure-induced inflammation in the liver and kidney by activating the oxidative stress pathway and modulating expression of NXRs to regulate related CYP450 isoforms, ultimately leading to histopathological injury in the liver and kidney, whereas sodium butyrate ameliorated this injury. These results offer novel insights into the molecular mechanisms underlying the protective effects of sodium butyrate in mitigating T-2 toxin-induced hepatorenal injury in juvenile quails. PRACTICAL APPLICATION: The mechanisms of T-2 toxin toxicity have been well described in experimental animals, but studies in birds are limited. With the development of society, the market scale of quails farming has been expanding, and the value of quails meat and eggs is increasing; there is an urgent need to clarify the harm of T-2 toxin to quails and its mechanism.

Multi-platform analysis revealed the substance basis and mechanism of Wei-Tong-Xin in ameliorating ENS dysfunction for dyspepsia treatment

Ethnopharmacological relevanceDuodenal motility disorder is a contributing factor to dyspepsia. The traditional Chinese medicine (TCM) formula Wei-Tong-Xin (WTX), originated from the famous ancient Chinese formula “Wan Ying Yuan”, has been demonstrated efficacy in alleviating dyspepsia. Aim of the studyThe current study aims to elucidate the chemical composition of WTX to establish the pharmacodynamic material basis. On the basis of component, in depth to illuminate the mechanism by which WTX treats dyspepsia via constructing the comprehensive analysis of multi-platform. Materials and methodsThe chemical constituents of WTX were systematically analyzed by UHPLC-Q-TOF-MS/MS data processing methods. Based on this, network pharmacology was employed to predict the mechanism by which WTX improved dyspepsia. The dyspepsia mouse model was constructed, and histopathology as well as intestinal permeability were assessed using H&E staining, PAS staining and FITC-dextran assay. Protein expression was detected using Western blot, immunofluorescence, immunohistochemistry and ELISA kits. ResultsA total of 100 chemical components of WTX were preliminarily identified. Network pharmacological analysis indicated that the therapeutic mechanism of WTX in treating dyspepsia may be related to the regulation of inflammation and oxidative stress-related signaling pathways. In vivo studies showed that WTX mitigated duodenal inflammation and oxidative stress responses, repairing the intestinal mucosal barrier damaged by cisplatin (CIS). Additionally, WTX restored the number of glial cells diminished by inflammatory damage, and ameliorated the serotoninergic neuronal dysfunction caused by insufficient secretion of glia-derived neurotrophic factor (GDNF), and enhanced intestinal transit. ConclusionsIn this study, a total of 100 components of the WTX extract were identified through literature review and mass spectrometry database search. Utilizing computer technology, in conjunction with pharmacodynamic and mechanistic studies, WTX has been found to restore serotoninergic neuronal function by reducing intestinal mucosal inflammatory and oxidative damage, ultimately promoting intestinal transport and treating dyspepsia.

Oxysophocarpine attenuates inflammatory osteolysis by modulating the NF-κb pathway and the reactive oxygen species-related Nrf2 signaling pathway.

Inflammatory diseases often result in bone loss due to persistent inflammation, which activates osteoclasts and increases bone resorption. Oxysophocarpine (OSC), a bioalkaloid extracted from the roots of Sophora japonica and other leguminous plants, has neuroprotective and anti-tumor properties. However, it is still uncertain whether OSC can effectively inhibit the differentiation of osteoclasts and bone resorption. Therefore, this study explored the potential role of OSC in osteoclast formation and inflammatory osteolysis and its underlying mechanisms. This study involved inducing primary mouse bone marrow macrophages (BMMs) into osteoclasts using macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL) and examined the effects of OSC on osteoclast (OC) differentiation, function, and intracellular reactive oxygen species (ROS) production. The impact of OSC on the expression of osteoclast-specific genes and inflammation-related factors was assessed using real-time quantitative PCR. Additionally, changes in oxidative stress-related factors, NF-κB, and MAPK signaling pathways were examined using western blotting. Finally, this study investigated the influence of OSC on a mouse cranial bone resorption model induced by titanium (Ti) particles in vivo. OSC inhibited OC differentiation and resorption and reduces intracellular ROS levels. Moreover, OSC suppressed IL-1β, TNF-α, IL-6, and osteoclast-specific gene transcription while increasing Nrf2 and HO-1 protein expression. Furthermore, OSC inhibited the expression and autoregulation of the NFATc1 gene, ultimately leading to a reduction in Ti particle-induced bone resorption in mice. OSC could be regarded as an innovative medication for the treatment of osteoclast-associated inflammatory osteolytic diseases.

Ginkgo biloba extract inhibits hippocampal neuronal injury caused by mitochondrial oxidative stress in a rat model of Alzheimer's disease.

Ginkgo biloba extracts (GBE) have been shown to effectively improve cognitive function in patients with Alzheimer's disease (AD). One potential therapeutic strategy for AD is to prevent loss of adult hippocampal neurons. While recent studies have reported that GBE protects against oxidative stress in neurons, the underlying mechanisms remain unclear. In this study, an AD-like rat model was established via bidirectional injection of amyloid beta 25-35 (Aβ25-35; 20 μg) in the hippocampal CA1 region. Learning and memory abilities of experimental rats were AD assessed in response to oral administration of 7.5 g/L or 15 g/L Ginkgo biloba extract 50 (GBE50) solution and the peroxidation phenomenon of hippocampal mitochondria determined via analysis of mitochondrial H2O2 and several related enzymes. Levels of the oxidative stress-related signaling factor cytochrome C (Cyto C), apoptosis-related proteins (Bax, Bcl-2 and caspase-3) and caspase-activated DNase (CAD) were further detected via western blot. 8-Hydroxydeoxyguanosine (8-OHdG), the major product of DNA oxidative stress, was evaluated to analyze DNA status. Our results showed elevated H2O2 levels and monoamine oxidase (MAO) activity, and conversely, a decrease in the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus of AD rats. Administration of GBE50 regulated the activities of these three enzymes and induced a decrease in H2O2. GBE50 exerted regulatory effects on abnormally expressed apoptotic proteins in the AD rat hippocampus, enhancing the expression of Bcl-2, inhibiting release of Cyto C from mitochondria, and suppressing the level of caspase-3 (excluding cleaved caspase-3). Furthermore, GBE50 inhibited DNA damage by lowering the generation of 8-OHdG rather than influencing expression of CAD. The collective findings support a protective role of GBE50 in hippocampal neurons of AD-like animals against mitochondrial oxidative stress.

Identification of candidate genes and molecular mechanisms related to asthma progression using bioinformatics

BackgroundAsthma is a heterogeneous disorder. This study aimed to identify changes in gene expression and molecular mechanisms associated with moderate to severe asthma.MethodsDifferentially expressed genes (DEGs) were analyzed in GSE69683 dataset among moderate asthma and its controls as well as between severe asthma and moderate asthma. Key module genes were identified via co-expression analysis, and the molecular mechanism of the module genes was explored through enrichment analysis and gene set enrichment analysis (GSEA). GSE89809 was used to verify the characteristic genes related to moderate and severe asthma.ResultsAccordingly, 2540 DEGs were present between moderate asthma and the control group, while 6781 DEGs existed between severe asthma and moderate asthma. These genes were identified into 14 co-expression modules. Module 7 had the highest positive correlation with severe asthma and was recognized to be a key module by STEM. Enrichment analysis demonstrated that the module genes were mainly involved in oxidative stress-related signaling pathways. The expression of HSPA1A, PIK3CG and PIK3R6 was associated with moderate asthma, while MAPK13 and MMP9 were associated with severe asthma. The AUC values were verified by GSE89809. Additionally, 322 drugs were predicted to target five genes.ConclusionThese results identified characteristic genes related to moderate and severe asthma and their corresponding molecular mechanisms, providing a basis for future research.

Identification of Oxidative Stress-Related Biomarkers for Pain-Depression Comorbidity Based on Bioinformatics.

Oxidative stress has been identified as a major factor in the development and progression of pain and psychiatric disorders, but the underlying biomarkers and molecular signaling pathways remain unclear. This study aims to identify oxidative stress-related biomarkers and signaling pathways in pain-depression comorbidity. Integrated bioinformatics analyses were applied to identify key genes by comparing pain-depression comorbidity-related genes and oxidative stress-related genes. A total of 580 differentially expressed genes and 35 differentially expressed oxidative stress-related genes (DEOSGs) were identified. By using a weighted gene co-expression network analysis and a protein-protein interaction network, 43 key genes and 5 hub genes were screened out, respectively. DEOSGs were enriched in biological processes and signaling pathways related to oxidative stress and inflammation. The five hub genes, RNF24, MGAM, FOS, and TKT, were deemed potential diagnostic and prognostic markers for patients with pain-depression comorbidity. These genes may serve as valuable targets for further research and may aid in the development of early diagnosis, prevention strategies, and pharmacotherapy tools for this particular patient population.

Neighborhood Disadvantage and Prostate Tumor RNA Expression of Stress-Related Genes

African American men experience greater prostate cancer incidence and mortality than White men. Growing literature supports associations of neighborhood disadvantage, which disproportionately affects African American men, with aggressive prostate cancer; chronic stress and downstream biological impacts (eg, increased inflammation) may contribute to these associations. To examine whether several neighborhood disadvantage metrics are associated with prostate tumor RNA expression of stress-related genes. This cross-sectional study leveraged prostate tumor transcriptomic data for African American and White men with prostate cancer who received radical prostatectomy at the University of Maryland Medical Center between August 1992 and January 2021. Data were analyzed from May 2023 to April 2024. Using addresses at diagnosis, 2 neighborhood deprivation metrics (Area Deprivation Index [ADI] and validated bayesian Neighborhood Deprivation Index) as well as the Racial Isolation Index (RI) and historical redlining were applied to participants' addresses. Self-reported race was determined using electronic medical records. A total of 105 stress-related genes were evaluated with each neighborhood metric using linear regression, adjusting for race, age, and year of surgery. Genes in the Conserved Transcriptional Response to Adversity (CTRA) and stress-related signaling genes were included. A total of 218 men (168 [77%] African American, 50 [23%] White) with a median (IQR) age of 58 (53-63) years were included. African American participants experienced greater neighborhood disadvantage than White participants (median [IQR] ADI, 115 [100-130] vs 92 [83-104]; median [IQR] RI, 0.68 [0.34-0.87] vs 0.11 [0.06-0.14]). ADI was positively associated with expression for 11 genes; HTR6 (serotonin pathway) remained significant after multiple-comparison adjustment (β = 0.003; SE, 0.001; P < .001; Benjamini-Hochberg q value = .01). Several genes, including HTR6, were associated with multiple metrics. We observed higher expression of 5 proinflammatory genes in the CTRA with greater neighborhood disadvantage (eg, CXCL8 and ADI, β = 0.008; SE, 0.003; P = .01; q value = .21). In this cross-sectional study, the expression of several stress-related genes in prostate tumors was higher among men residing in disadvantaged neighborhoods. This study is one of the first to suggest associations of neighborhood disadvantage with prostate tumor RNA expression. Additional research is needed in larger studies to replicate findings and further investigate interrelationships of neighborhood factors, tumor biology, and aggressive prostate cancer to inform interventions to reduce disparities.

MyC Factor Analogue CO5 Promotes the Growth of Lotus japonicus and Enhances Stress Resistance by Activating the Expression of Relevant Genes.

The symbiotic relationship between arbuscular mycorrhizal fungi (AMF) and plants is well known for its benefits in enhancing plant growth and stress resistance. Research on whether key components of the AMF colonization process, such as MyC factors, can be directly utilized to activate plant symbiotic pathways and key functional gene expression is still lacking. In this paper, we found that, using a hydroponics system with Lotus japonicus, MyC factor analogue chitin oligomer 5 (CO5) had a more pronounced growth-promoting effect compared to symbiosis with AMF at the optimal concentration. Additionally, CO5 significantly enhanced the resistance of Lotus japonicus to various environmental stresses. The addition of CO5 activated symbiosis, nutrient absorption, and stress-related signaling pathways, like AMF symbiosis, and CO5 also activated a higher and more extensive gene expression profile compared to AMF colonization. Overall, the study demonstrated that the addition of MyC factor analogue CO5, by activating relevant pathways, had a superior effect on promoting plant growth and enhancing stress resistance compared to colonization by AMF. These findings suggest that utilizing MyC factor analogues like CO5 could be a promising alternative to traditional AMF colonization methods in enhancing plant growth and stress tolerance in agriculture.